Congenital Amegakaryocytic Thrombocytopenia (CAMT)

What is Congenital Amegakaryocytic Thrombocytopenia (CAMT)

It tends to show an autosomal recessive inheritance. The gene involved is the MPL gene, a gene which codes for TPO receptors. TPO is essential for megakaryocytic proliferation. They eventually give rise to platelets. TPO receptor is also needed for maturation and preventing apoptosis in the other hematopoietic stem cells. As the age advances, there is increased apoptosis happening of the erythroid and the myeloid cells.

Types of CAMT

There are basically two types of CAMT

Type 1 CAMT and type 2 CAMT

Type 1 CAMT

More severe form

Caused by nonsense mutation in the mpl gene due to this no functional TPO receptor is formed. They tend to have severe thrombocytopenia in infancy, and they tend to develop pancytopenia very early (within 3-4 years of onset of thrombocytopenia).

Type 2 CAMT

Less severe. Caused due to missense mutation happening in the MPL gene. They will have thrombocytopenia but a mild and relatively less dramatic course.

Clinical Features

There will always be in the neonatal period, these children will have thrombocytopenia. It will manifest in the form of petechiae, purpura, epistaxis. As the age advances, in the first decade of life, they all develop pancytopenia. Also, the features of anemia and recurrent infection due to leukopenia. Some patients of type 2 CAMT, tend to develop a slight elevation in platelet count beyond infancy. It does not affect the likelihood of progression to pancytopenia but this is a change that can be seen in the patients.

In 20% cases of CAMT other congenital anomalies, basically involving 2 organ systems CNS and the cardiovascular system. In CNS, cerebellar and cerebral hypoplasia is found and they will also have delayed milestones. In the cardiovascular system, there is an increased risk of congenital heart disease VSD, ASD, PDA, and Coarctation of Aorta.

Laboratory Findings

The platelet count will be low and in patients with one pancytopenia there will fall in the Hb and TLC. In addition, they will have elevation in HbF and macrocytosis, and macrocytic RBCs. BM will show, there is a severe reduction in the megakaryocytes in all individuals. Those with pancytopenia will also have a reduction in other hematopoietic lineages.

Diagnosis and Complications

• Clinical patterns and BM findings
• Mutational analysis can be done - called as the gold standard
• Complications can progress to MDS/AML, many of them are positive for Monosomy 7 or Trisomy 8

Learning Points: CAMT Vs Immune Thrombocytopenia

In CAMT, on platelet transfusion, there is an adequate response to it. There is improvement in bleeding manifestation till the time circulating platelets are sufficient in the circulation. There will be no response to corticosteroids. In Immune thrombocytopenia, Platelets transfusion will show inadequate or no response. There will be a response to corticosteroids.

Treatment

• HSCT is the therapy of choice
• For symptomatic management the platelet transfusion can be done
• Platelet transfusion is single-donor, leuko-reduced
• Use irradiated, CMV-free blood products
• In CAMT type 2, can use TPO agonists that are Eltrombopag/Romiplostim- Partial response.
• Their use should be limited because there is an increased risk of fibrosis and increased progression to AML/MDS.

Hope you found this blog helpful for your E-learning for NEET SS Pediatrics. For more informative and interesting posts like these, keep reading PrepLadder’s blogs. 

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